This invention pertains to a process for the preparation of esters of carboxylic acids. More particularly, the present invention pertains to a process wherein a solution of a carboxylic acid in a first solvent and an alcohol are fed to a simulated moving bed reactor (SMBR) containing a solid(s) to produce a first stream comprising a solution of an ester of the carboxylic acid and the alcohol and a second stream comprising the first solvent contained in the alcohol. The solid(s) present in the SMBR facilitates the esterification reaction and the separation of the first solvent from the carboxylic acid.
Due to their importance as commercial products, numerous esters of carboxylic acids are produced on a large scale in the chemical industry. The reaction of an alcohol and a carboxylic acid to form an ester is accompanied by the formation of a molecule of water. Since esterification reactions are generally reversible reactions under conditions of acid catalysis, the water molecule produced by esterification and the ester reverse react to form the alcohol and the carboxylic acid, thus limiting the equilibrium conversion of the carboxylic acid. If any water is present along with the carboxylic acid, it will further limit the extent of esterification. Homogenous acid catalysts frequently are used to catalyze the esterification. The removal of the acid catalyst at the end of the reaction requires additional processing steps.
The esterification of 2-keto-L-gulonic acid (KLG) in the overall process of manufacturing ascorbic acid is an example of an important commercial esterification process. Known commercial processes for the production of ascorbic acid comprise four major sections: (1) a fermentation section wherein a sugar such as glucose or sorbose is subjected to fermentation to produce 2-keto-L-gulonic acid (KLG); (2) the purification and isolation of anhydrous KLG; (3) the conversion of the isolated KLG to an alkyl KLG ester (AKLG) by esterification with an alcohol, typically methanol, and (4) cyclization of the AKLG using stoichiometric amounts of a base to produce L-ascorbic acid. This process has evolved from the original Reichstein Process (T. Reichstein, A. Grussner, Helv. Chim. Acta 17, p. 311, 1934). In traditional processes employed for the production of ascorbic acid from fermentation-derived KLG, the KLG is isolated as a solid from the aqueous fermentation broth by crystallization and drying. Since esterification reactions are equilibrium limited, the isolated KLG normally must be free of water to obtain an acceptable yield of the ester of KLG in the subsequent esterification step. Evaporation of water to obtain dry KLG requires substantial energy and the equipment required to evaporate the water increases the capital cost.
If KLG monohydrate is utilized instead of anhydrous KLG, additional steps to remove the water of hydration are required during the esterification, such as described in Published PCT Patent Application WO 99/03853. Furthermore, during crystallization of KLG, a significant amount of KLG present in the mother liquor stream may not be recovered. Apart from any water that is present in the KLG solids utilized to make the ester, water formed during the esterification reaction limits the equilibrium conversion. Any unreacted KLG results in lost yield. If a homogenous acid catalyst, such as sulfuric acid or hydrochloric acid, is used to catalyze the esterification of KLG ester, removal of the acidic catalysts or salts thereof becomes necessary. Thus, the processes presently employed in the manufacture of ascorbic acid have a number of disadvantages such as (1) high energy requirement and high capital and operating costs occasioned by the isolation of dry KLG, (2) yield loss during the purification of KLG, (3) incomplete conversion of KLG to its ester in the presence of water which is formed during esterification and/or present in the KLG as a result of the KLG manufacturing process, and (4) removal of the homogenous acid esterification catalyst.
Numerous improvements to the traditional processes for the manufacture of ascorbic acid are described in the literature. To address the energy and capital costs involved in isolating dry KLG solids, a process to exchange solvents by simultaneously removing water and adding methanol is proposed in U.S. Pat. No. 6,146,534. In the solvent exchange process described in the ""534 patent, an aqueous stream of a carboxylic acid is fed to a simulated moving bed (SMB) unit packed with a basic resin. An organic solvent such as methanol is used as the separating agent to produce (1) a product stream containing the carboxylic acid in the solvent and substantially free of water and (2) a waste stream containing water in methanol. A similar solvent exchange process for dewatering KLG is disclosed in U.S. Pat. No. 6,153,791. The aqueous KLG feed stream contains a significant amount of sugar, e.g., sorbose, remaining from the fermentation as impurity, which also is removed along with the aqueous waste stream thus purifying the KLG. In both processes, though a substantial amount of water is removed from the aqueous KLG solution, some water is present in the organic solvent stream containing KLG. Since the processes disclosed in both the ""534 and ""791 patents accomplish separation only, an additional step to esterify KLG is required. During the esterification step, the residual water from the separation step and the water formed during the reaction limit the equilibrium conversion of KLG to its ester. The removal of the homogenous acid catalyst used for the esterification is still required.
The extent of esterification can be increased by simultaneously removing water or the ester as the reaction proceeds. WO 9903853 discloses that the esterification of KLG may be carried out in a 2-stage process in which the reaction can be driven to completion by crystallization of methyl 2-keto-L-gulonate coupled with efficient removal of water. This process requires multiple crystallization stages and solid liquid separation equipment. German Patent Application DE 199 38 980 A1 discloses a method for producing C1-C10 alkyl KLG esters by the esterification of KLG with a C1-C10 alcohol in the presence of an acid catalyst, wherein the esterification is carried out in a liquid film on a hot surface with simultaneous removal of water. This process is simple to operate but requires significant energy and large volumes of alcohol solvent to act as a carrier for water removal. This process does not provide a means to remove impurities. Other known means to enhance the extent of esterification include membrane reactors for the selective removal of water during esterifications described, for example, by Feng and Huang, Studies of a Membrane Reactor: Esterification Facilitated By Pervaporation, Chemical Engineering Science, Vol. 51, No. 20, pp. 4673-4679, 1996; Jennings et al U.S. Pat. No. 2,956,070; Okomoto et al, Pervaporation-aided Esterification of Oleic Acid, Journal of Chemical Engineering of Japan, Vol. 26, No 5, pages 475-481,1993; Kwon, et al, Removal of Water Produced from Lipase-Catalyzed Esterification in Organic Solvent by Pervaporation, Biotechnology and Bioengineering, Vol. 46, pp. 393-395, 1995; Keurentjes, The Esterification of Tartaric Acid with Ethanol: Kinetics and Shifting the Equilibrium by Means of Pervaporation, xe2x80x9cChemical Engineering Science, Vol. 49, No. 24A, pages 4681-4689,1994; and Xiuyuam, et al, Modified Aromatic Polyimide Membrane Preparation and Pervaporation Results for Esterification System,xe2x80x9d Water Treatment, 10, pages 115-120, 1995. Simulated Moving Bed Reactors have been proposed as another alternative to enhance the extent of esterifications. See, for example, Kawase et al., Increased Esterification Conversion By Application Of The Simulated Moving-Bed Reactor, Chemical Engineering Science, Vol. 51, No 11, pages 2971-2976, 1996; Mazzotti et al., Dynamics Of A Chromatographic Reactor: Esterification Catalyzed By Acidic Resins, Ind. Eng. Chem. Res. 1997, 36, 3163-3172; and U.S. Pat. No. 5,405,992. These publications propose processes that remove water formed during esterification of a carboxylic acid. The process provided by the present invention differs from these disclosures in that it accomplishes a solvent exchange while simultaneously removing water formed during esterification.
Esters of KLG may be produced from KLG monohydrate in anhydrous methanol using sulfuric acid or other strong acid catalysts. If homogenous acids are used, the removal of the acid or salts thereof is required. For example, U.S. Pat. No. 5,391,770 describes a series of steps consisting of esterification of KLG with methanol in the presence of a strong soluble acid followed by a cyclization with an inorganic base and protonation with sulfuric acid. This is a lengthy process and requires crystalline KLG monohydrate and nearly anhydrous conditions to effect esterification and cyclization. U.S. Pat. No. 5,744,634 (European Patent Application EP 0 671 405 A) discloses a process for the production of the methyl or ethyl ester of KLG by esterification of KLG with methanol or ethanol in the presence of an ion exchange resin. The esterification process takes place in a tubular reactor containing an ion exchange resin using a residence time of from 10 to 120 minutes. The process disclosed in U.S. Pat. No. 5,744,634 requires the monohydrate or, preferably, the anhydrous form to esterify KLG with methanol or ethanol.
The present invention provides a means to prepare an ester of a carboxylic acid utilizing an alcohol and a solution of a carboxylic acid in a first solvent wherein (1) the first solvent present in the carboxylic acid feed is removed, (2) some or all of any impurities present in the carboxylic acid feed may be removed, (3) the conversion of the carboxylic acid to its ester is enhanced by simultaneously removing water, and (4) the need to use, remove, and dispose of a homogenous acid catalyst normally used to esterify the carboxylic acid is eliminated. The present invention provides a process for the preparation of a solution of a carboxylic acid ester which comprises the steps of:
I. feeding (i) a carboxylic acid in the form of a solution comprising the carboxylic acid and a first solvent; (ii) an alcohol; and (iii) a second solvent which is miscible with the first solvent, to a simulated moving bed reactor containing a solid that is water and alcohol insoluble, catalyzes the esterification of the carboxylic acid, and has different affinities for the carboxylic acid and the first solvent; wherein the carboxylic acid and alcohol react to form a carboxylic acid ester; and
II. removing from the simulated moving bed reactor (i) a first liquid stream comprising a solution of the carboxylic acid ester in the second solvent and (ii) a second liquid stream comprising the first solvent and water formed during esterification of the carboxylic acid.
A preferred embodiment of the present invention is represented by a process for the preparation of an alkanol solution of an alkyl 2-keto-L-gulonate ester by the steps comprising:
I. feeding (i) an aqueous solution of 2-keto-L-gulonic acid (KLG) and (ii) an alkanol to a simulated moving bed reactor containing a strong acid cation exchange resin that is water and alcohol insoluble, catalyzes the esterification of the carboxylic acid, and has different affinities for KLG and water, wherein the KLG and alkanol react to form an alkyl 2-keto-L-gulonate ester (AKLG); and
II. removing from the simulated moving bed reactor (i) a first liquid stream comprising a solution of the AKLG in the alkanol and (ii) a second liquid stream comprising water derived from the aqueous solution of KLG of step I. and water formed during the reaction of the KLG and alkanol.
Our novel process yields greater than equilibrium conversions of carboxylic acids to carboxylic acid esters such as alkyl carboxylates by separating the carboxylic acid ester from water. In accordance with the above-described preferred embodiment of our novel process, the ester of 2-keto-L-gulonic acid is removed as a solution in the alkanol and may be converted to ascorbic by acid cyclization or a variation of the Reichstein process. Water that is formed during esterification and that is present in the KLG feed, e.g., a KLG-containing fermentation broth, is removed as a waste stream from the simulated moving bed reactor. Some impurities which may be present in KLG-containing fermentation broths may be removed in the aqueous waste stream. The alkanol present in the waste stream can be recovered by various methods such as distillation.